Abstract | OBJECTIVES: Immuno-gene therapy of mesothelioma with an adenovirus encoding interferon-beta mediated strong antitumor responses in murine models with low but not high tumor burden. Our goals were to determine the mechanisms responsible for this loss of efficacy and to test the hypothesis that the combination of preoperative adenovirus encoding interferon-beta and surgical resection would be effective in treating bulky tumors. METHODS: Flank tumors of a mouse mesothelioma cell line were treated with adenovirus encoding interferon-beta or adenoviral vector encoding the bacterial protein beta-galactosidase. Cytotoxic T lymphocytes and tumor infiltration by T lymphocytes were measured. Tumors were surgically excised 72 hours later and tumor cells were injected in the contralateral flank to create a model of a metastatic focus. Tumor-free survival and distant metastatic disease were assessed. RESULTS: CONCLUSIONS: The use of adenovirus encoding interferon-beta or surgical debulking alone is ineffective in treating large tumors, but combining preoperative adenovirus encoding interferon-beta and surgical debulking significantly reduces tumor recurrence and improves long-term tumor-free survival. We postulate that adenovirus encoding interferon-beta amplifies the cytotoxic T-lymphocyte antitumor response, allowing elimination of residual tumor cells.
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Authors | Robert J Kruklitis, Sunil Singhal, Peter Delong, Veena Kapoor, Daniel H Sterman, Larry R Kaiser, Steven M Albelda |
Journal | The Journal of thoracic and cardiovascular surgery
(J Thorac Cardiovasc Surg)
Vol. 127
Issue 1
Pg. 123-30
(Jan 2004)
ISSN: 0022-5223 [Print] United States |
PMID | 14752422
(Publication Type: Comparative Study, Journal Article)
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Chemical References |
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Topics |
- Adenoviridae
- Animals
- Biopsy, Needle
- Cell Line, Tumor
- Combined Modality Therapy
- Disease Models, Animal
- Female
- Gene Transfer Techniques
- Genetic Therapy
(methods)
- Immunohistochemistry
- Immunotherapy
(methods)
- Interferon-beta
(pharmacology)
- Mesothelioma
(mortality, pathology, surgery, therapy)
- Mice
- Mice, Inbred BALB C
- Preoperative Care
- Random Allocation
- Sensitivity and Specificity
- Survival Rate
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